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The molecular origins of mucosal vulnerability to cancer

Reference	BBS/E/F/00042212
Principal Investigator / Supervisor	Dr Ian Johnson
Co-Investigators / Co-Supervisors	Professor Clare Mills, Dr Claudio Nicoletti
Institution	Quadram Institute Bioscience
Department	Quadram Institute Bioscience Department
Funding type	Research
Value (£)	1,837,850
Status	Completed
Type	Institute Project
Start date	01/04/2005
End date	31/03/2010
Duration	60 months

Abstract

The general objectives of this project are to advance our understanding of the intestinal mucosa as an integrated biological system, influenced simultaneously by food components, systemic metabolism and the colonic microbiota, to explore the effects of nutrition and gut bacteria on early precancerous changes in the colon and oesophagus, and to determine the role of cell proliferation and apoptosis in the maintenance of gut health. Having previously obtained evidence for changes in protein expression in colorectal mucosa that are consistent with a field abnormality predisposing individuals to the emergence of cancer, we now propose that this heightened vulnerability to neoplasia is linked to the chronic state of low-grade systemic inflammation that characterizes the metabolic syndrome. Furthermore we have evidence that the ensuing adverse changes in gene expression are caused in part by aberrant methylation of CpG-islands. Nutritional factors act on the colorectal mucosa for decades prior to the emergence of localised lesions via the adenoma-carcinoma sequence. We will use proteomic techniques to define early diet-related patterns of protein expression associated with vulnerability to colorectal cancer in more detail. We will also explore the impact of dietary and microbiological variables on the rate and gene-specificity of CpG-island methylation in animal models and humans. Specifically we aim to identify and isolate differentially expressed proteins from human volunteers, and quantify patterns of methylation affecting genes associated with disordered Wnt signalling, and transcriptional silencing of the S100A4 gene.

Summary

unavailable

Committee	Closed Committee - Agri-food (AF)
Research Topics	Ageing, Diet and Health, Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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